Toll-like receptors: Insights into their possible role in the pathogenesis of Lyme neuroborreliosis
Toll-like receptors: Insights into their possible role in the pathogenesis of Lyme neuroborreliosis
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DOI：
10.1128/iai.00394-08
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发表时间：
2008-10-01
影响因子：
3.1
通讯作者：
Philipp, Mario T.
中科院分区：
文献类型：
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作者：
Bernardino, Andrea L. F.;Myers, Tereance A.;Philipp, Mario T.
莱姆神经型疏螺旋体病可能是由壁虱传播的伯氏疏螺旋体对神经系统的炎症作用引起的。小胶质细胞是中枢神经系统(CNS)中驻留的巨噬细胞，在启动对微生物产物的免疫反应中起着重要作用。此外，星形胶质细胞是中枢神经系统的主要胶质细胞类型，也可能导致脑部炎症。TLRs(Toll样受体)被神经胶质细胞用来识别病原体相关分子模式(PAMPs)，介导先天反应，并启动获得性免疫反应。我们推测，由于PAMP的特异性，TLR1、-2、-5和-9可能参与了莱姆氏疏螺旋体病的发病机制。此前的报道显示，恒河猴是唯一出现莱姆氏神经疏螺旋体病迹象的动物模型。因此，我们使用原代培养的恒河猴星形胶质细胞和小胶质细胞来确定TLRs在介导对伯氏杆菌的促炎反应中的作用。结果表明，小胶质细胞和星形胶质细胞对伯氏杆菌的反应是通过TLR1/2和TLR5实现的。此外，我们观察到小胶质细胞对伯氏杆菌的吞噬作用不仅增强了TLR1、-2和-5的表达，而且还增强了TLR4的表达。综上所述，我们的数据证明了星形胶质细胞和小胶质细胞TLR1、-2和-5参与了灵长类神经胶质细胞对伯氏假单胞菌的体内反应。这些TLR介导的反应所引发的致炎分子可能是莱姆氏疏螺旋体病发病机制中的重要因素。
Lyme neuroborreliosis is likely caused by inflammatory effects of the tick-borne spirochete Borrelia burgdorferi on the nervous system. Microglia, the resident macrophage cells within the central nervous system (CNS), are important in initiating an immune response to microbial products. In addition, astrocytes, the major CNS glial cell type, also can contribute to brain inflammation. TLRs (Toll-like receptors) are used by glial cells to recognize pathogen-associated molecular patterns (PAMPs), mediate innate responses, and initiate an acquired immune response. Here we hypothesize that because of their PAMP specificities, TLR1, -2, -5, and -9 may be involved in the pathogenesis of Lyme neuroborreliosis. Previous reports have shown that the rhesus monkey is the only animal model to exhibit signs of Lyme neuroborreliosis. Therefore, we used primary cultures of rhesus astrocytes and microglia to determine the role of TLRs in mediating proinflammatory responses to B. burgdorferi. The results indicate that microglia and astrocytes respond to B. burgdorferi through TLR1/2 and TLR5. In addition, we observed that phagocytosis of B. burgdorferi by microglia enhances not only the expression of TLR1, -2, and -5, but also that of TLR4. Taken together, our data provide proof of the concept that astrocyte and microglial TLR1, -2, and -5 are involved in the in vivo response of primate glial cells to B. burgdorferi. The proinflammatory molecules elicited by these TLR-mediated responses could be a significant factor in the pathogenesis of Lyme neuroborreliosis.